The evidence for an association between coxsackievirus B (CVB) infection, pancreatic islet autoimmunity, and clinical type 1 diabetes is increasing. Results from prospective cohorts and pancreas histopathology studies have provided a compelling case. However, the demonstration of a causal relationship is missing, and is likely to remain elusive until tested in humans by avoiding exposure to this candidate viral trigger. To this end, CVB vaccines have been developed and are entering clinical trials. However, the progress made in understanding the biology of the virus and in providing tools to address the long-standing question of causality contrasts with the scarcity of information about the antiviral immune responses triggered by infection. Beta-cell death may be primarily induced by CVB itself, possibly in the context of poor immune protection, or secondarily provoked by T-cell responses against CVB-infected beta cells. The possible involvement of epitope mimicry mechanisms skewing the physiological antiviral response toward autoimmunity has also been suggested. We here review the available evidence for each of these 3 non-mutually exclusive scenarios. Understanding which ones are at play is critical to maximize the odds of success of CVB vaccination, and to develop suitable tools to monitor the efficacy of immunization and its intermingling with autoimmune onset or prevention.

中文翻译：

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柯萨奇病毒和 1 型糖尿病：糖尿病发生机制和预防意义。

越来越多的证据表明柯萨奇 B 型病毒 (CVB) 感染、胰岛自身免疫和临床 1 型糖尿病之间存在关联。前瞻性队列和胰腺组织病理学研究的结果提供了令人信服的案例。然而，因果关系的证据缺失，并且在通过避免接触这种候选病毒触发因素进行人体测试之前，这种关系可能仍然难以捉摸。为此，CVB疫苗已经研发出来，并正在进入临床试验。然而，在了解病毒生物学和提供解决长期存在的因果关系问题的工具方面取得的进展与感染引发的抗病毒免疫反应的信息匮乏形成鲜明对比。β细胞死亡可能主要是由 CVB 本身诱导的，可能是在免疫保护较差的情况下，或由针对 CVB 感染的 β 细胞的 T 细胞反应继发引起。也有人提出可能涉及表位拟态机制，使生理抗病毒反应偏向自身免疫。我们在此回顾这 3 种非互斥情景中每一种情景的可用证据。了解哪些因素在发挥作用对于最大限度地提高 CVB 疫苗接种的成功率以及开发合适的工具来监测免疫效果及其与自身免疫发作或预防的混合至关重要。